Craig J. Goergen

Influences of Aortic Motion and Curvature on Vessel Expansion in Murine Experimental Aneurysms

Objective—To quantitatively compare aortic curvature and motion with resulting aneurysm location, direction of expansion, and pathophysiological features in experimental abdominal aortic aneurysms (AAAs). Methods and Results—MRI was performed at 4.7 T with the following parameters: (1) 3D acquisition for vessel geometry and (2) 2D cardiac-gated acquisition to quantify luminal motion. Male 24-week-old mice were imaged before and after AAA formation induced by angiotensin II (AngII)–filled osmotic pump implantation or infusion of elastase. AngII-induced AAAs formed near the location of maximum abdominal aortic curvature, and the leftward direction of expansion was correlated with the direction of suprarenal aortic motion. Elastase-induced AAAs formed in a region of low vessel curvature and had no repeatable direction of expansion. AngII significantly increased mean blood pressure (22.7 mm Hg, P<0.05), whereas both models showed a significant 2-fold decrease in aortic cyclic strain (P<0.05). Differences in patterns of elastin degradation and localization of fluorescent signal from protease-activated probes were also observed. Conclusion—The direction of AngII aneurysm expansion correlated with the direction of motion, medial elastin dissection, and adventitial remodeling. Anterior infrarenal aortic motion correlated with medial elastin degradation in elastase-induced aneurysms. Results from both models suggest a relationship between aneurysm pathological features and aortic geometry and motion.

Increased Anterior Abdominal Aortic Wall Motion: Possible Role in Aneurysm Pathogenesis and Design of Endovascular Devices

PURPOSE To determine whether variations in aortic wall motion exist in mammalian species other than humans and to consider the potential implications of such variations. METHODS M-mode ultrasound was used to measure abdominal aortic wall motion in 4 animal species [mice (n=10), rats (n=8), rabbits (n=7), and pigs (n=5)], and humans (n=6). Anterior wall displacement, posterior wall displacement, and diastolic diameter were measured. The ratio of displacement to diameter and cyclic strain were calculated. RESULTS Body mass varied from 24.1+/-2.4 g (mouse) to 61.8+/-13.4 kg (human); aortic diameter varied from 0.53+/-0.07 mm (mouse) to 1.2+/-1 mm (human). Anterior wall displacement was 2.5 to 4.0 times greater than posterior among the species studied. The ratios of wall displacement to diastolic diameter were similar for the anterior (range 9.40%-11.80%) and posterior (range 2.49%-3.91%) walls among species. The ratio of anterior to posterior displacement (range 2.47-4.03) and aortic wall circumferential cyclic strain (range 12.1%-15.7%) were also similar. An allometric scaling exponent was experimentally derived relating anterior wall (0.377+/-0.032, R2=0.94) and posterior wall (0.378+/-0.037, R2=0.93) displacement to body mass. CONCLUSION Abdominal aortic wall dynamics are similar in animals and humans regardless of aortic size, wih more anterior than posterior wall motion. Wall displacement increases linearly with diameter, but allometrically with body mass. These data suggest increased dynamic strain of the anterior wall. Increased strain, corresponding to increased elastin fatigue, may help explain why human abdominal aortic aneurysms initially develop anteriorly. Aortic wall motion should be considered when developing endovascular devices, since asymmetric motion may affect device migration, fixation, and sealing.

In Vivo Quantification of Murine Aortic Cyclic Strain, Motion, and Curvature: Implications for Abdominal Aortic Aneurysm Growth

To develop methods to quantify cyclic strain, motion, and curvature of the murine abdominal aorta in vivo.

Emerging Trends in Heart Valve Engineering: Part I. Solutions for Future

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed.

Assessing breast tumor margin by multispectral photoacoustic tomography

An unmet need exists in high-speed and highly-sensitive intraoperative assessment of breast cancer margin during conservation surgical procedures. Here, we demonstrate a multispectral photoacoustic tomography system for breast tumor margin assessment using fat and hemoglobin as contrasts. This system provides ~3 mm tissue depth and ~125 μm axial resolution. The results agreed with the histological findings. A high sensitivity in margin assessment was accomplished, which opens a compelling way to intraoperative margin assessment.

Optical coherence tractography using intrinsic contrast

Organs such as the heart and brain possess intricate fiber structures that are best characterized with three-dimensional imaging. For instance, diffusion-based, magnetic resonance tractography (MRT) enables studies of connectivity and remodeling during development and disease macroscopically on the millimeter scale. Here we present complementary, high-resolution microscopic optical coherence imaging and analysis methods that, when used in conjunction with clearing techniques, can characterize fiber architecture in intact organs at tissue depths exceeding 1 mm. We anticipate that these techniques can be used to study fiber architecture in situ at microscopic scales not currently accessible to diffusion magentic resonance (MR), and thus, to validate and complement macroscopic structural imaging techniques. Moreover, as these techniques use intrinsic signals and do not require tissue slicing and staining, they can be used for high-throughput, nondestructive evaluation of fiber architecture across large tissue volumes.

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell–Mediated Ureteritis and Hydronephrosis

Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10+ regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell–mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell–derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs.

Fluorochrome‐Functionalized Magnetic Nanoparticles for High‐Sensitivity Monitoring of the Polymerase Chain Reaction by Magnetic Resonance

Easy to find: magnetic nanoparticles bearing fluorochromes (red) that intercalate with DNA (green) form microaggregates with DNA generated by the polymerase chain reaction (PCR). These aggregates can be detected at low cycle numbers by magnetic resonance (MR).

Molecular Imaging of Experimental Abdominal Aortic Aneurysms

Current laboratory research in the field of abdominal aortic aneurysm (AAA) disease often utilizes small animal experimental models induced by genetic manipulation or chemical application. This has led to the use and development of multiple high-resolution molecular imaging modalities capable of tracking disease progression, quantifying the role of inflammation, and evaluating the effects of potential therapeutics. In vivo imaging reduces the number of research animals used, provides molecular and cellular information, and allows for longitudinal studies, a necessity when tracking vessel expansion in a single animal. This review outlines developments of both established and emerging molecular imaging techniques used to study AAA disease. Beyond the typical modalities used for anatomical imaging, which include ultrasound (US) and computed tomography (CT), previous molecular imaging efforts have used magnetic resonance (MR), near-infrared fluorescence (NIRF), bioluminescence, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Mouse and rat AAA models will hopefully provide insight into potential disease mechanisms, and the development of advanced molecular imaging techniques, if clinically useful, may have translational potential. These efforts could help improve the management of aneurysms and better evaluate the therapeutic potential of new treatments for human AAA disease.

Emerging Trends in Heart Valve Engineering: Part IV. Computational Modeling and Experimental Studies

In this final portion of an extensive review of heart valve engineering, we focus on the computational methods and experimental studies related to heart valves. The discussion begins with a thorough review of computational modeling and the governing equations of fluid and structural interaction. We then move onto multiscale and disease specific modeling. Finally, advanced methods related to in vitro testing of the heart valves are reviewed. This section of the review series is intended to illustrate application of computational methods and experimental studies and their interrelation for studying heart valves.